Clinical and patient (pt)-reported outcomes (PROs) in a phase 3, randomized, open-label study evaluating axicabtagene ciloleucel (axi-cel) versus standard-of-care (SOC) therapy in elderly pts with relapsed/refractory (R/R) large B-cell lymphoma (LBCL; ZUMA-7).
Authors: Jason Westin, Frederick L. Locke, Michael Dickinson, Armin Ghobadi, Mahmoud Elsawy, Tom van Meerten, David Bernard Miklos, Matthew Ulrickson, Miguel-Angel Perales, Umar Farooq, Luciano Wannesson, Lori Ann Leslie, Marie José Kersten, Caron Alyce Jacobson, John M. Pagel, Gerald Wulf, Linqiu Du, Julia Snider, Christina Ann To, Olalekan O. Oluwole
Journal: Journal of Clinical Oncology (2022)

7548 Background: Elderly pts with R/R LBCL are at risk of inferior outcomes, increased toxicity, and inability to tolerate second-line (2L) SOC treatment (Tx) (Di M, et al. Oncologist. 2021). Further 2L SOC Tx is often associated with poor health-related quality of life (QoL) (Lin V, et al. J Clin Oncol . 2020;38:e20070). In the pivotal Phase 3 ZUMA-7 study, we assessed outcomes, including PROs, of 2L axi-cel (an autologous anti-CD19 CAR T-cell therapy) versus SOC in elderly pts with R/R LBCL. Methods: Pts aged ≥65 y were assessed in a planned subgroup analysis. Pts with ECOG PS 0-1 and R/R LBCL ≤12 mo after 1L chemoimmunotherapy (CIT) were randomized 1:1 to axi-cel or SOC (2-3 cycles of platinum-based CIT; pts with partial or complete response [CR] proceeded to HDT-ASCT). PRO instruments, including the EORTC QLQ-C30 (Global Health [GH] and Physical Functioning [PF]) and the EQ-5D-5L VAS, were administered at timepoints including baseline (BL; prior to Tx), Day (D) 50, D100, D150, and Month (M) 9, then every 3 mo up to 24 mo or time of event-free survival event (EFS), whichever occurred first. The QoL analysis set included all pts who had a BL PRO and ≥1 completed measure at D50, D100, or D150. A clinically meaningful change was defined as 10 points for each EORTC QLQ-C30 score, 7 points for EQ-5D-5L VAS score. Results: As of 03/18/2021, 51 and 58 elderly pts were randomized to the axi-cel and SOC arms, respectively, with median ages (range) of 70 y (65-80) and 69 y (65-81). At BL, more axi-cel versus SOC pts had high-risk features, including 2L age-adjusted IPI 2-3 (53% vs 31%) and elevated LDH (61% vs 41%). EFS was superior with axi-cel versus SOC (HR, 0.276, P&lt; 0.0001), with higher CR rates (75% vs 33%). Grade ≥3 Tx-emergent adverse events (AEs) occurred in 94% and 82% of axi-cel and SOC pts, respectively, and Grade 5 Tx-related AEs occurred in 0 and 1 pt. In the QoL analysis set comprising 46 axi-cel and 42 SOC pts, there were statistically significant and clinically meaningful differences in mean change of scores from BL at D100 favoring axi-cel for EORTC QLQ-C30 GH ( P&lt;0.0001) and PF ( P=0.0019) and EQ-5D-5L VAS ( P&lt;0.0001). For all 3 domains, scores also favored ( P&lt;0.05) axi-cel over SOC at D150. The mean estimated scores numerically returned to or exceeded BL scores earlier in the axi-cel arm (by D150) but never equaled or exceed BL scores by M15 in the SOC arm. Conclusions: Axi-cel demonstrated superiority over 2L SOC in pts ≥65 y with significantly improved EFS and a manageable safety profile. Compared with SOC, axi-cel also showed meaningful improvement in QoL over SOC, measured by multiple validated PRO instruments, with suggested faster recovery to pre-Tx QoL. The superior clinical outcomes and pt experience with axi-cel over SOC should help inform Tx choices in 2L R/R LBCL for pts ≥65 y. Clinical trial information: NCT03391466.